The effectiveness of pollen allergen immunotherapy on allergic rhinitis over 18 years: A national cohort study in Denmark.

BACKGROUND: Because long-term effectiveness of pollen allergen immune therapy (AIT) for allergic rhinitis (AR) is not well-described, we studied effectiveness over 18 years in Denmark. METHODS: A register-based cohort study using data on filled prescriptions, 1995-2016, Denmark. In a cohort of 1.1 million intranasal corticosteroid inhaler users (proxy for AR), we matched users treated with grass, birch or mugwort AIT 1:2 with non-treated users on baseline year and 24 characteristics in the 3 years prior to baseline. The primary outcome was the odds ratio (OR) of using anti-allergic nasal inhaler during the pollen season in the treated versus non-treated group by years since baseline. RESULTS: Among 7760 AR patients treated with pollen AIT, the OR of using nasal inhaler 0-5 years after baseline was reduced when compared with 15,520 non-treated AR individuals (0-2 years, OR 0.84 (0.81-0.88); 3-5 years, OR 0.88 (0.84-0.92)), but was close to unity or higher thereafter (6-9 years, OR 1.03 (0.97-1.08); 10-18 years, OR 1.18 (1.11-1.26)). In post hoc analyses, results were more consistent for those who already had 3 of 3 baseline years of use, and in patients using nasal inhaler in the latest pollen season (0-2 years, OR 0.76 (0.72-0.79); 3-5 years OR 0.86 (0.81-0.93); 6-9 years, OR 0.94 (0.87-1.02); 10-18 years, OR 0.94 (0.86-1.04)) as opposed to no such use. CONCLUSIONS: Patients treated with pollen AIT in routine care to a higher degree stopped using anti-allergic nasal inhaler 0-5 years after starting the standard 3 years of therapy, and not beyond 5 years. Post hoc analyses suggested effectiveness was more consistent among patients with persistent AR.

Post-acute symptoms 4 months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study.

Post-acute symptoms are not uncommon after SARS-CoV-2 infection with pre-Omicron variants. How Omicron and COVID-19 booster vaccination influence the risk of post-acute symptoms is less clear. We analyzed data from the nationwide Danish questionnaire study EFTER-COVID comprising 44,553 individuals ≥15 years old, tested between July 2021 and January 2022, in order to evaluate the association of the Omicron variant and COVID-19 booster vaccination with post-acute symptoms and new-onset general health problems, four months after infection with SARS-CoV-2. Risk differences (RDs) were estimated by comparing Omicron -cases to controls, Omicron to Delta -cases, and Omicron vaccinated cases with three to -two doses, adjusted for age, sex, BMI, self-reported chronic diseases, Charlson comorbidity index, healthcare occupation, and vaccination status. Four months after testing for SARS-CoV-2 during the Omicron period, cases experienced substantial post-acute symptoms and new-onset health problems compared to controls; the largest RD was observed for memory issues (RD=7.2%, 95%CI: 6.4 to 8.1). However, risks were generally lower than in the Delta period, particularly for dysosmia (RD=-15.0%, 95%CI: -17.0 to -13.2) and dysgeusia (RD=-11.2%, 95%CI: -13.2 to -9.5). Booster vaccination was associated with fewer post-acute symptoms and new-onset health problems, four months after Omicron infection, compared to two COVID-19 vaccine doses.

A standardised protocol for relative SARS-CoV-2 variant severity assessment, applied to Omicron BA.1 and Delta in six European countries, October 2021 to February 2022.

Several SARS-CoV-2 variants that evolved during the COVID-19 pandemic have appeared to differ in severity, based on analyses of single-country datasets. With decreased testing and sequencing, international collaborative studies will become increasingly important for timely assessment of the severity of new variants. Therefore, a joint WHO Regional Office for Europe and ECDC working group was formed to produce and pilot a standardised study protocol to estimate relative case-severity of SARS-CoV-2 variants during periods when two variants were co-circulating. The study protocol and its associated statistical analysis code was applied by investigators in Denmark, England, Luxembourg, Norway, Portugal and Scotland to assess the severity of cases with the Omicron BA.1 virus variant relative to Delta. After pooling estimates using meta-analysis methods (random effects estimates), the risk of hospital admission (adjusted hazard ratio (aHR) = 0.41; 95% confidence interval (CI): 0.31-0.54), admission to intensive care unit (aHR = 0.12; 95% CI: 0.05-0.27) and death (aHR = 0.31; 95% CI: 0.28-0.35) was lower for Omicron BA.1 compared with Delta cases. The aHRs varied by age group and vaccination status. In conclusion, this study demonstrates the feasibility of conducting variant severity analyses in a multinational collaborative framework and adds evidence for the reduced severity of the Omicron BA.1 variant.

Molecular epidemiology of the SARS-CoV-2 variant Omicron BA.2 sub-lineage in Denmark, 29 November 2021 to 2 January 2022.

Following emergence of the SARS-CoV-2 variant Omicron in November 2021, the dominant BA.1 sub-lineage was replaced by the BA.2 sub-lineage in Denmark. We analysed the first 2,623 BA.2 cases from 29 November 2021 to 2 January 2022. No epidemiological or clinical differences were found between individuals infected with BA.1 versus BA.2. Phylogenetic analyses showed a geographic east-to-west transmission of BA.2 from the Capital Region with clusters expanding after the Christmas holidays. Mutational analysis shows distinct differences between BA.1 and BA.2.

Chronic hyperglycemia, hypercholesterolemia, and metabolic syndrome are associated with risk of tendon injury.

Tendon injury is a considerable problem affecting both physically active and sedentary people. The aim of this study was to examine the relationship between markers for metabolic disorders (hyperglycemia, hypercholesterolemia, and metabolic syndrome) and the risk of developing tendon injuries requiring referral to a hospital. The Copenhagen City Heart Study is a prospective study of diabetic and non-diabetic individuals from the Danish general population with different physical activity levels. The cohort was followed for 3 years via national registers with respect to tendon injuries. Data from 5856 individuals (median age 62 years) were included. The overall incidence of tendon injury in both upper and lower extremities that required an out-patient or in-house visit to a hospital was ~5.7/1000 person years. Individuals with elevated HbA1c (glycated hemoglobin) even in the prediabetic range (HbA1c>5.7%) had a ~3 times higher risk of tendon injury in the lower extremities only, as compared to individuals with normal HbA1C levels. Hypercholesterolemia (total cholesterol>5 mmol/L) increased risk of tendon injury in the upper extremities by ~1.5 times, and individuals with metabolic syndrome had ~2.5 times higher risk of tendon injury in both upper and lower extremities. In conclusion, these data demonstrate for the first time in a large cohort with different physical activity levels that the indicators for metabolic syndrome are a powerful systemic determinant of tendon injury, and two of its components, hyperglycemia and hypercholesterolemia, each independently make tendons susceptible for damage and injury.

Retrospective markers of paediatric atopic dermatitis persistence after hospital diagnosis: A nationwide cohort study.

BACKGROUND: Atopic dermatitis (AD) normally onsets in childhood and mostly resolves before adolescences. Disease persistence is known to be difficult to study properly, and current predictors are insufficient to identify more than a small fraction of patients at risk. OBJECTIVE: To study personal AD medicine history as a retrospective marker of persistent AD. METHODS: The study population included all Danish first hospital contacts with a diagnosis of AD (ICD-10, L20) between 1995 and 2012. National register data following the diagnosis were used to define persistent AD activity until 2017 according to personal AD medicine history before diagnosis. Activity was defined as filled prescriptions for topical corticosteroids (TCS) or calcineurin inhibitors (TCI), dermatologist contacts or hospital re-contacts for AD. Risk ratios (RR) for persistent activity (defined as activity >4 of the most recent 5 years) were estimated according to AD medicine history (prescriptions filled prior to diagnosis) adjusted for age at onset, parental AD and basic covariates. RESULTS: A total of 13 628 patients were diagnosed at ages 0-16 years and had up to 21 years of follow-up. 10 years after diagnosis, 67% showed activity (9.5% persistent). Among prior TCS users (69%), the RR10y of persistent activity increased 1- to 6-fold with increasing strength of strongest TCS/TCI ever, and with number of TCS courses. Prior use of antibiotics (RR10y 1.32, 95% CI 1.09-1.59) and antihistamines (RR10y 1.65, 95% CI 1.42-1.91) increased the RR10y in a dose-dependent manner. In >90% of patients, prior medication use occurred <4 years before diagnosis. CONCLUSIONS AND CLINICAL RELEVANCE: The strength and type of AD medication used in the previous 4 years may predict 10-year persistence of AD. Since children may be misjudged as having milder disease when seen between flares of skin lesions, this information may improve physicians' ability to determine the correct prognosis independently of current AD severity.

Increased Risk of Inflammatory Bowel Disease in Families with Tonsillectomy: A Danish National Cohort Study.

BACKGROUND: The possible etiologic link between tonsillectomy and inflammatory bowel diseases remains unclear. To investigate the hereditary component, we assessed the risk of inflammatory bowel disease after own tonsillectomy as well as after tonsillectomy among family members. METHODS: A nationwide Danish cohort of 7,045,288 individuals was established and linked to comprehensive national registers with data on kinship, tonsillectomy surgery, and diagnosis of inflammatory bowel disease from all health sectors. We used Poisson regression models to estimate hospital contact rate ratios (RR) for Crohn's disease and ulcerative colitis, with 95% confidence intervals (CI), between individuals with or without tonsillectomy, as well as between individuals with or without tonsillectomized relatives. RESULTS: During 189 million person-years of follow-up between 1977 and 2014, 276,673 individuals were tonsillectomized, 22,015 developed Crohn's disease, and 49,550 developed ulcerative colitis. Rates of inflammatory bowel disease were elevated up to 20 years after own tonsillectomy (Crohn's disease: RR 1.52 [95% CI = 1.43, 1.61]; ulcerative colitis: RR 1.24 [95% CI = 1.18, 1.29]). RRs for Crohn's disease was 1.22 (95% CI = 1.17, 1.27) after first-degree relatives' tonsillectomy, 1.14 (95% CI = 1.08, 1.19) after second-degree relatives' tonsillectomy, and 1.08 (95% CI = 1.01, 1.15) after third-degree relatives' tonsillectomy. Corresponding RRs for ulcerative colitis were 1.10 (95% CI = 1.07, 1.13), 1.05 (95% CI = 1.01, 1.08), and 1.03 (95% CI = 0.98, 1.09). CONCLUSIONS: Even individuals with tonsillectomized family members were at increased risk of inflammatory bowel disease. These findings call into question a direct influence of tonsillectomy on gastrointestinal inflammation and point instead toward shared hereditary or environmental factors. See video abstract at, http://links.lww.com/EDE/B464.

Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy.

BACKGROUND: Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered. OBJECTIVE: To identify common genetic variants associated with tonsillectomy. METHODS: We used tonsillectomy information from Danish health registers and carried out a genome-wide association study comprising 1464 patients and 12 019 controls of Northwestern European ancestry, with replication in an independent sample set of 1575 patients and 1367 controls. RESULTS: The variant rs2412971, intronic in HORMAD2 at chromosome 22q12.2, was robustly associated with tonsillectomy (OR=1.22; p=1.48×10-9) and is highly correlated with SNPs previously found to be associated with IgA nephropathy, Crohn's disease (CD) and early onset inflammatory bowel disease (IBD). The risk allele for tonsillectomy corresponded to increased risk of IgA nephropathy and decreased risk of CD and IBD. We further performed lookup analyses of the top SNP for outcomes related to tonsillectomy in the combined discovery and replication sample and found that rs2412971 was associated with acute tonsillitis (OR=1.19; p=7.82×10-4), chronic disease of the tonsils (OR=1.19; p=2.32×10-6) and appendectomy (OR=1.18; p=1.13×10-3). CONCLUSIONS: We identified and replicated a genetic association at 22q12.2 with tonsillectomy. Further functional investigation is required to illuminate whether the molecular mechanisms underlying the genetic association involve general lymphoid hyper-reaction throughout the mucosa-associated lymphoid tissue system.

Prevalence of atopic dermatitis in infants by domestic water hardness and season of birth: Cohort study.

BACKGROUND: Atopic dermatitis (AD) appears to be more common in regions with hard domestic water and in children with a fall/winter birth. However, it is unknown whether a synergistic effect exists. OBJECTIVE: We sought to evaluate the association between domestic water hardness and season of birth, respectively, with onset of AD within the first 18 months of life in a large Danish birth cohort. METHODS: Of children from the Danish National Birth Cohort, 52,950 were included. History of physician-diagnosed AD and population characteristics were obtained from interviews. Birth data were obtained from the Civil Registration System, and domestic water hardness data were obtained from the Geological Survey of Denmark and Greenland. The relative prevalence (RP) of AD was calculated by using log-linear binomial regression. RESULTS: The prevalence of AD was 15.0% (7,942/52,950). The RP of AD was 5% (RPtrend, 1.05; 95% CI, 1.03-1.07) higher for each 5° increase in domestic water hardness (range, 6.60-35.90 German degrees of hardness [118-641 mg/L]). Although the RP of AD was higher in children with a fall (RP, 1.24; 95% CI, 1.17-1.31) or winter (RP, 1.18; 95% CI, 1.11-1.25) birth, no significant interaction was observed with domestic water hardness. The population attributable risk of hard domestic water on AD was 2%. CONCLUSION: We observed that early exposure to hard domestic water and a fall/winter birth was associated with an increase in the relative prevalence of AD within the first 18 months of life. Although the 2 exposures did not interact synergistically, a dose-response relationship was observed between domestic water hardness and AD.

Age at Menarche and Risk of Multiple Sclerosis: A Prospective Cohort Study Based on the Danish National Birth Cohort.

Few studies have addressed the possible association between age at menarche and multiple sclerosis (MS), and results are conflicting. We studied this issue in a large prospective cohort study. The study cohort comprised 77,330 women included in the Danish National Birth Cohort (1996-2002). Information on menarcheal age was ascertained at the first interview, which took place in the 16th week of pregnancy. Women were followed for MS from the first interview to December 31, 2011. Associations between age at menarche and risk of MS were evaluated with hazard ratios and 95% confidence intervals using Cox proportional hazards regression models. Overall, 226 women developed MS during an average follow-up period of 11.7 years. Age at menarche among women with MS was generally lower than that among women without MS (Wilcoxon rank-sum test; P = 0.002). We observed an inverse association between age at menarche and MS risk. For each 1-year increase in age at menarche, risk of MS was reduced by 13% (hazard ratio = 0.87, 95% confidence interval: 0.79, 0.96). Early age at menarche appears to be associated with an increased risk of MS. The mechanisms behind this association remain to be established.

Self-rated health in women prior to clinical onset of multiple sclerosis: A study within the Danish National Birth Cohort.

BACKGROUND: It has been suggested that onset of multiple sclerosis (MS) is preceded by a clinically silent period of up to 10 years. OBJECTIVES: Examine whether such a period should be associated with poor self-rated health (SRH). METHODS: Information on SRH before pregnancy was ascertained among 80,848 women participating in the Danish National Birth Cohort (DNBC) 1996-2002. Women were followed for MS from enrolment in DNBC in the 16th week of pregnancy until 31 December 2011. Associations between SRH and MS were evaluated by means of hazard ratios (HR) with 95% confidence intervals (CIs) using Cox proportional hazard models. RESULTS: During on average 11.7 years of follow-up, 239 women were diagnosed with MS. Overall, neither women with fair (HR = 1.09 (95% CI = 0.83-1.41), n = 113) nor poor pre-pregnancy SRH (HR = 0.94 (95% CI = 0.47-1.87), n = 9) were at an increased risk of MS compared with women reporting very good pre-pregnancy SRH. Supplementary analyses showed no significant differences in MS risk in consecutive periods of follow-up. CONCLUSION: In this first prospective cohort study assessing MS risk as a function of SRH, we found no indication of a long period of poor SRH prior to MS. Our findings based on pregnant women may not necessarily apply to all women.

Filaggrin genotype and skin diseases independent of atopic dermatitis in childhood.

BACKGROUND: Filaggrin gene (FLG) mutations compromise skin barrier functions and increase risk of atopic dermatitis. We aimed to study effects on other skin diseases using unique data from the Danish registers. METHODS: FLG genotyping of a population-based sample of 1547 children with extracted DNA and information on skin diseases from the Danish National Birth Cohort and Health Register, with 18 years follow-up during years 1996-2013. Odds ratios (OR) and hazard ratios (HR) were estimated using logistic regression and Cox regression, respectively, and adjusted for physician-diagnosed atopic dermatitis. RESULTS: FLG mutations were associated with increased risk of dry skin (OR 1.9, CI 1.1-3.1), and a decreased risk of fungal skin infections at age <18 months (OR 0.2, CI 0.1-0.8). There was no association with wart treatments (HR 1.0, CI 0.6-1.7). FLG mutations were associated with an increased risk of atopic dermatitis (OR 3.3, CI 2.1-5.3), dermatology consultations for allergy or rash (HR 2.2, CI 1.4-3.5), basic dermatology consultations at age <5 years (HR 2.2, CI 1.7-2.9), urticaria at age <18 months (OR 2.9, CI 1.0-7.9), and other rash at age <18 months (OR 2.1, CI 1.2-3.8). CONCLUSIONS: FLG mutations may predispose to skin disease in young children including urticaria, and rash not recognized as atopic dermatitis although equally frequent. In clinical practice, FLG genotyping may help indicate the use of moisturizers to reduce skin problems.

Common filaggrin gene mutations and risk of cervical cancer.

BACKGROUND: As carriers of filaggrin gene (FLG) mutations may have a compromised cervical mucosal barrier against human papillomavirus infection, our primary objective was to study their risk of cervical cancer. METHODS: We genotyped 586 cervical cancer patients for the two most common FLG mutations, R501X and 2282del4, using blood from the Copenhagen Hospital Biobank, Denmark. Controls (n = 8050) were genotyped in previous population-based studies. Information on cervical cancer, mortality and emigration were obtained from national registers. Odds ratios (OR) were estimated by logistic regression with adjustment for age at blood sampling, and weighted by the genotype-specific inverse probability of death between diagnosis and sampling. Hazard ratios (HR) were estimated by Cox regression with time since diagnosis as underlying time, and with adjustment for age at diagnosis and stratification by cancer stage. RESULTS: The primary results showed that FLG mutations were not associated with the risk of cervical cancer (6.3% of cases and 7.7% of controls were carriers; OR adjusted 0.81, 95% CI 0.57-1.14; OR adjusted+ weighted 0.96, 95% CI 0.58-1.57). Among cases, FLG mutations increased mortality due to cervical cancer (HR 4.55, 95% CI 1.70-12.2), however, the association was reduced after stratification by cancer stage (HR 2.53, 95% CI 0.84-7.59). CONCLUSION: Carriage of FLG mutations was not associated with the risk of cervical cancer.

Major stressful life events in adulthood and risk of multiple sclerosis.

OBJECTIVE: It is unclear whether psychological stress is associated with increased risk of multiple sclerosis (MS). We studied the association between major stressful life events and MS in a nationwide cohort study using death of a child or a spouse or marital dissolution as indicators of severe stress. METHODS: We created two study cohorts based on all Danish men and women born 1950-1992. One cohort consisted of all persons who became parents between 1968 and 2010, and another cohort consisted of all persons who married between 1968 and 2010. Members of both cohorts were followed for MS between 1982 and 2010 using data from the National Multiple Sclerosis Registry. Associations between major stressful life events and risk of MS were evaluated by means of MS incidence rate ratios (RR) with 95% confidence interval (CI) obtained in Poisson regression analyses. RESULTS: During approximately 30 million person-years of follow-up, bereaved parents experienced no unusual risk of MS compared with parents who did not lose a child (RR=1.12 (95% CI 0.89 to 1.38)). Likewise, neither divorced (RR=0.98 (95% CI 0.89 to 1.06)) nor widowed (RR=0.98 (95% CI 0.71 to 1.32) persons were at any unusual risk of MS compared with married persons of the same sex. CONCLUSIONS: Our national cohort study provides little evidence for a causal association between major stressful life events (as exemplified by divorce or the loss of a child or a spouse) and subsequent MS risk.

Helminth therapy (worms) for induction of remission in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, globally-occurring gastrointestinal disorder and a major cause of illness and disability. It is conventionally classified into Crohn's disease (CD) and ulcerative colitis (UC). Helminths are parasitic worms with complex life cycles involving tissue- or lumen-dwelling stages in their hosts, and causing long-lasting or chronic infections that are frequently asymptomatic. Helminths modulate immune responses of their hosts, and many observational and experimental studies support the hypothesis that helminths suppress immune-mediated chronic inflammation that occurs in asthma, allergy and IBD. OBJECTIVES: The objective was to evaluate the efficacy and safety of helminth treatment for induction of remission in IBD. SEARCH METHODS: We searched the following databases from inception to 13 July 2013: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register. We also searched four online trials registries, and abstracts from major meetings. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) where the intervention was any helminth species or combination of helminth species, administered in any dose and by any route and for any duration of exposure to people with active CD or UC, confirmed through any combination of clinical, endoscopic and histological criteria were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed eligibility using a standardized data collection form. We used the RevMan software for analyses. The primary outcome was induction of remission as defined by the included studies. Secondary outcomes included clinical, histologic, or endoscopic improvement as defined by the authors, endoscopic mucosal healing, change in disease activity index score, change in quality of life score, hospital admissions, requirement for intravenous corticosteroids, surgery, study withdrawal and the incidence of adverse events. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We calculated the mean difference (MD) and 95% CI for continuous outcomes. We assessed the methodological quality of included studies using the Cochrane risk of bias tool. The overall quality of the evidence supporting each outcome was assessed using the GRADE criteria. MAIN RESULTS: Two RCTs (90 participants) were included. One trial assessed the efficacy and safety of Trichuris suis (T. suis) ova in patients with UC (n = 54). The other RCT was a phase one that assessed the safety and tolerability of T. suis ova in patients with CD (n = 36). The risk of bias in both studies was judged to be low. In the UC study, during the 12-week study period, participants in the active arm received 2-weekly aliquots of 2500 T. suis eggs, added to 0.8 mL of saline; those in the placebo arm received 0.8 mL saline only. There were sparse data available for the outcomes clinical remission and clinical improvement. Ten per cent (3/30) of patients in the T. suis arm entered remission compared to 4% (1/24) of patients in the placebo arm (RR 2.40, 95% CI 0.27 to 21.63). Forty-three per cent (13/30) of patients in the T. suis group achieved clinical improvement compared to 17% (4/24) of placebo patients (RR 2.60, 95% CI 0.97 to 6.95). The mean ulcerative colitis disease activity index (UCDAI) score was lower in the T. suis group (6.1 +/- 0.61) compared to the placebo group (7.5 +/- 0.66) after 12 weeks of treatment (MD -1.40, 95% CI -1.75 to -1.05). There was only limited evidence relating to the proportion of patients who experienced an adverse event. Three per cent (1/30) of patients in the T. suis group experienced at least one adverse event compared to 12% (3/24) of placebo patients (RR 0.27, 95% CI 0.03 to 2.40). None of the adverse events reported in this study were judged to be related to the study treatment. GRADE analyses rated the overall quality of the evidence for the primary and secondary outcomes (i.e. clinical remission and improvement) as low due to serious imprecision. In the CD study, participants received a single treatment of T. suis ova at a dosage of 500 (n = 9), 2500 (n = 9), or 7500 (n = 9) embryonated eggs or matching placebo (n = 9). The CD study did not assess clinical remission or improvement as outcomes. There were sparse data on adverse events at two weeks. Thirty-seven per cent (10/27) of patients in the T. suis group experienced at least one adverse event compared to 44% (4/9) of placebo patients (RR 0.83, 95% CI 0.35 to 2.01). Only one adverse event (dysgeusia) was judged to be possibly related to treatment in this study. Dysgeusia was reported in one patient in the T. suis group and in one patient in the placebo group. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to allow any firm conclusions regarding the efficacy and safety of helminths used to treat patients with IBD. The evidence for our primary efficacy outcomes in this review comes from one small study and is of low quality due to serious imprecision. We do not have enough evidence to determine whether helminths are safe when used in patients with UC and CD. Further RCTs are required to assess the efficacy and safety of helminth therapy in IBD.

Maternal obesity, gestational weight gain, and risk of asthma and atopic disease in offspring: a study within the Danish National Birth Cohort.

BACKGROUND: High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are suggested to influence risk of asthma and atopic disease in offspring. OBJECTIVE: We examined the effect of BMI and GWG on risk of asthma, wheezing, atopic eczema (AE), and hay fever in children during the first 7 years of life. METHODS: This was a cohort study of 38,874 mother-child pairs from the Danish National Birth Cohort (enrollment 1996-2002) with information from the 16th week of pregnancy and at age 6 months, 18 months, and 7 years of the child. Odds ratios (ORs) with 95% CIs were calculated by logistic regression with adjustment for potential confounders. RESULTS: During the first 7 years of life, 10.4% of children developed doctor-diagnosed asthma, 25.8% AE, and 4.6% hay fever. Maternal BMI and to a lesser extent GWG were associated with doctor-diagnosed asthma ever. In particular, BMI≥35 (adjusted OR, 1.87; 95% CI, 0.95-3.68) and GWG≥25 kg (adjusted OR, 1.97; 95% CI, 1.38-2.83) were associated with current severe asthma at age 7 years. Maternal BMI was also associated with wheezing in offspring, with the strongest association observed between BMI≥35 and late-onset wheezing (adjusted OR, 1.87; 95% CI, 1.28-2.73). Maternal BMI and GWG were not associated with AE or hay fever. CONCLUSIONS: Maternal obesity during pregnancy was associated with increased risk of asthma and wheezing in offspring but not with AE and hay fever, suggesting that pathways may be nonallergic.

Cohort profile: EFTER-COVID - a Danish nationwide cohort for assessing the long-term health effects of the COVID-19 pandemic.

PURPOSE: To follow SARS-CoV-2-infected persons up to 18 months after a positive test in order to assess the burden and nature of post acute symptoms and health problems. PARTICIPANTS: Persons in Denmark above 15 years of age, who were tested positive for SARS-CoV-2 during 1 September 2020 to 21 February 2023 using a RT-PCR test. As a reference group, three test-negative individuals were selected for every two test-positive individuals by matching on test date. FINDINGS TO DATE: In total, 2 427 913 invitations to baseline questionnaires have been sent out and 839 528 baseline questionnaires (34.5%) have been completed. Females, the age group 50-69 years, Danish-born and persons, who had received at least one SARS-CoV-2 vaccination booster dose were more likely to participate. Follow-up questionnaires were sent at 2, 4, 6, 9, 12 and 18 months after the test, with response rates at 42%-54%. FUTURE PLANS: New participants have been recruited on a daily basis from 1 August 2021 to 23 March 2023. Data collection will continue until the last follow-up questionnaires (at 18 months after test) have been distributed in August 2024.

Relative vaccine protection, disease severity, and symptoms associated with the SARS-CoV-2 omicron subvariant BA.2.86 and descendant JN.1 in Denmark: a nationwide observational study.

BACKGROUND: During the 2023 Danish COVID-19 vaccination campaign, an updated monovalent mRNA vaccine targeting the SARS-CoV-2 omicron XBB.1.5 subvariant was administered. However, the rapid spread of a genetically divergent omicron BA.2.86 subvariant, JN.1, since September, 2023, poses potential challenges due to its rapid dominance and possible immune escape. Using national electronic health registry data from all regions of Denmark, we aimed to investigate whether the SARS-CoV-2 subvariant BA.2.86, and its descendant JN.1, differed from other circulating variants in terms of their ability to escape vaccine protection, the risk of infection leading to severe disease, and self-reported symptoms among infected people. METHODS: In this observational study, we included all residents of Denmark aged 65 years and older who tested positive for SARS-CoV-2 by PCR between Oct 1 and Dec 31, 2023, and for whom genomic data on the SARS-CoV-2 variant that had caused their infection were available. Data from clinical testing, sentinel, and self-sampling-based surveillance were linked with national electronic civil, vaccination, and hospitalisation registers. The relative protection of the XBB.1.5 updated COVID-19 vaccine against BA.2.86 infections versus infections with other variants was analysed in a case-only study, and the relative risk of hospitalisation in people infected with BA.2.86 versus other variants was analysed in a case-control study. Both analyses were adjusted for time, comorbidities, and previous vaccination history, among other potential confounders. Additionally, prevalence patterns in self-reported symptoms among people of all ages infected with SARS-CoV-2 were reported separately by subvariant. FINDINGS: Of the 7581 people in Denmark aged 65 years or older who tested positive for SARS-CoV-2 by PCR during the study period, 5882 (78%) samples were eligible for sequencing. 3862 (66%) of these passed quality control, were successfully sequenced, and the SARS-CoV-2 variant and subvariant identified, and these individuals were included in the study. Of these 3862 people, 2184 (57%) were infected with the BA.2.86 subvariant, including 1615 JN.1 infections. Participants infected with BA.2.86 had 1·52 (95% CI 1·25-1·86) times the odds, and those infected with JN.1 had 1·60 (1·27-2·02) times the odds, of having received the XBB.1.5 vaccine at least 7 days before their infection compared with participants infected with a non-BA.2.86 variant. The severity analysis showed no evidence of association between the infecting variant and the risk of COVID-19 hospitalisation (odds ratio 1·04 [95% CI 0·86-1·26] for BA.2.86 and 1·07 [0·85-1·34] for JN.1). Similarly, there was no evidence of differences in self-reported symptoms by variant strain. INTERPRETATION: Compared with other SARS-CoV-2 variants, BA.2.86 and the JN.1 sublineage were less sensitive to vaccine-induced immune protection from the XBB.1.5 updated COVID-19 vaccine; however, we found no evidence that infection with BA.2.86 or JN.1 resulted in increased disease severity or different symptom profiles. Although less effective against the new variants, XBB.1.5 vaccination remains protective and reduces the risk of infection and COVID-19 disease. FUNDING: The Danish Government and the EU's EU4Health programme.